Respiratory distress syndrome (RDS), also termed hyaline membrane disease, is the leading cause of death and disability among premature infants. Of the 230,000 to 250,000 infants born prematurely each year in the United States, 40,000 to 50,000 develop RDS; and of those who develop this disease, 5,000 to 8,000 die. The risk of RDS is less for infants born closer to full term. However, RDS occurs in up to 75% of infants born at less than 30 weeks of gestation (less than 1250 grams body weight). See generally R. Perelman and P. Farrell, Pediatrics 70, 570 (1982); D. Vidyasagar, in Hyaline Membrane Disease: Pathogenesis and Pathophysiology, 98 (L. Stern Ed. 1984).
RDS is caused by a deficiency in lung surfactant, a material ordinarily secreted onto the surface of lung alveoli. In the absence of surfactant, the alveoli tend to collapse during exhalation. Collapse can be avoided by mechanically ventilating the lungs. Nevertheless, even though premature infants often begin to secrete surfactant within 48 hours after birth, lung damage may have by this time already occurred due to the high oxygen concentrations and positive pressures of mechanical ventilation.
A number of groups have sought to develop surfactant formulations which can be used to treat or prevent RDS. Both human and bovine natural surfactants have been administered into the airways of newborn infants. See, e.g., J. Horbar et al., N. Eng. J. Med. 320, 959 (1989); R. Soll et al., Pediatric Res. 23, 425A (1988). Problems with such natural microorganisms are, however, potential contamination with microorganisms and potential sensitization of the patient to proteins therein. Accordingly, completely synthetic surfactants have been developed. See, e.g., U.S. Pat. No. 4,826,821 to Clements; U.S. Pat. No. 4,312,860 to Clements.
With natural and synthetic surfactant formulations now available, a current problem is how to best administer them to a patient. Such patients are typically maintained on a ventilator with a breathing tube, an endotracheal tube extending through the patient's mouth and larynx. The endotracheal tube is joined to a ventilator Y-piece (typically through an endotracheal tube adapter), the Y-piece is connected to a pair of patient tubes, and the patient tubes are connected to a ventilating unit. The ventilating unit cyclically forces oxygen-rich air into, and allows oxygen-depleted air to escape from, the patient's lungs. One approach others have taken to administering a surfactant formulation to such a patient is to remove the Y-piece from the endotracheal tube adapter, inject the formulation into the endotracheal tube adapter, and rejoin the Y-piece to the endotracheal tube adapter. Another approach others have taken is to remove the Y-piece from the endotracheal tube adapter, insert a canula into the endotracheal tube adapter, inject the formulation through the canula, remove the canula, and rejoin the endotracheal tube adapter to the Y-piece. In both cases ventilation of the patient is interrupted. In both cases a risk of infecting the patient through the opened breathing tube exists. In both cases duration of administration is limited by the length of time which ventilation may be safely interrupted; and in both cases there is a need for substantial manipulation of the patient. These problems are compounded when the patient is a premature infant, particularly a premature infant afflicted with RDS, as such patients are sensitive to even gentle handling and susceptible to infection. Indeed, some premature infants critically ill with RDS do not tolerate even a brief interruption of mechanical ventilation.
Accordingly, an object of the present invention is to provide a method of administering a pharmaceutical formulation (particularly a surfactant formulation) to a patient's lungs without interrupting ventilation of that patient.
Another object of the present invention is to provide a method of administering a pharmaceutical formulation to a patient's lungs which does not require opening the breathing tube of that patient.
Another object of the present invention is to provide a method of administering a pharmaceutical formulation to a patient's lungs with a minimal number of manipulative steps to which that patient must be subjected.